Before the Mexican Cartel came to Bolivia, there were many other Bolivian Cartels and it was El Sueño who killed its leaders one by one and slowly took over Bolivia. Their connection with key politicians ended up them controlling most of Bolivia but before they got control the cartel was at war with UNIDAD which engulfed the whole of Bolivia and in the end the government had to sign a secret peace treaty with the cartel saying, "If you stop killing our people, we will look the other way. "Since then the cartel grew with power spreading its influence across all of South America and soon tried to spread its influence to other countries.

With the cartel growing with power and earning 2 billion dollars a week from its production and sale of cocaine the cartel modernized by buying top of the line weapons from the black market, Humvees and armored SUVs outfitted with swivel-mounted miniguns, APC's, along with helicopters like the Little Bird and Black Hawk.

Santa Blanca was founded by El Sueño, a dangerous sicario who had a dream-hence the name El Sueño-of creating a narco-state. To accomplish this, Sueño came to Bolivia, and formed the Santa Blanca Cartel in 2008. The citizens were given two options: "silver or lead" - work for Santa Blanca, or be killed.

Pac Katari led a rebellion against the cartel. The rebellion has been growing since the beginning of Operation Kingslayer. This is because all of the work that the Ghost Team (Nomad) has done has been credited to The Rebellion to keep their presence unknown.

The cartel was infiltrated by the DEA agent Ricky Sandoval. After his cover was blown, the agent is killed and the US government initiates Operation Kingslayer to take down the cartel. A Ghost Recon led by Nomad is sent in and systematically works their way up to El Sueño.

In the Narco Road DLC, a parallel story to the main game, players take control of a Ghost infiltrator who joins one of the gangs inside the cartel in order to uncover the secretive head of their world-class smuggling operations.

Santa Blanca therefore becomes allies, and the new enemy becomes a rival gang.